The need to develop an accurate chair-side screening instrument for caries activity and caries risk has been long recognized and extensive research work has been done in this area without much success. Our study takes a new approach in solving this problem. This approach is founded on a novel model, the Caries Risk Pyramid (CRP), which summarizes the available knowledge regarding the biology of dental caries. HYPOTHESIS: Based on the CRP model, we hypothesize that measuring the ability of dental plaque and/or saliva to generate alkali from urea, or other salivary substrates, together with the ability to generate acid from sugars, can provide an accurate estimation of an individual's caries status and possibly future caries risk because they summarize the combined effect of other caries risk factors. OBJECTIVE: In order to test this hypothesis we have developed an array of novel, chair-side tests for measuring acid and alkali generation in plaque and in saliva. The objective of this study is to assess the reliability and validity of these tests as screening tools for dental caries and to explore possible ways of combining the results of these tests in order to accurately identify individuals with caries. To accomplish this objective, a cross-sectional study on 200 adult subjects is proposed. SIGNIFICANCE: The proposed tests are novel because they consider the ability to generate alkali in plaque as a potential caries risk factor, which has not been previously included in existing multivariate risk assessment models. They are of low cost and give faster results compared to available biological caries risk tests. They do not require dental expertise, which makes them suitable for use by non-dental professionals. Once the tests have been validated in adults, our ultimate goal is to validate them in children and infants as screening tools for Early Childhood Caries (ECC), and ultimately as a predictor of future caries risk, either independently, or in combination with other caries risk factors. Another important potential application for the proposed tests would be the comparison of pre- to post- intervention risk in clinical dental practice, in research, and in community interventions. PUBLIC HEALTH RELEVANCE: Dental caries affects more than 50% of the children (ages 5 to 9 years) and 84% of the adults in the USA and it has a significant impact on the health, quality of life, and on the economy. The prevalence of dental caries is higher in certain ethnic minority populations and in individuals of low socioeconomic status and for that reason the disease is considered as an important health disparity. Interestingly, while the prevalence of dental caries has been declining slowly over the past thirty years in the United States, this decline has not been observed in the youngest age groups, those of 2 to 5 years. These facts demonstrate that the generalized measures currently available for caries prevention and management are not effective for all individuals and that there is a need to identify and address novel risk factors in high-risk populations. The proposed study is significant because it addresses this important issue. The objective of the study is to validate a new method for identifying individuals who have dental caries, or who are at risk to develop caries in the near future. This method consists of an array of simple tests that can be performed chair-side. The innovation of the method is that these tests measure risk factors that have not been previously considered in the existing caries risk assessment models. The advantages of the proposed tests are low cost and much faster results compared to available caries risk tests. More importantly, they do not require any dental expertise, which makes them suitable for use by non-dental professionals. Once the tests have been validated in adults, our ultimate goal is to validate them in children and infants as screening tools for Early Childhood Caries (ECC), and ultimately as a predictor of future caries risk, either independently, or in combination with other caries risk factors. They could be used by pediatricians and school nurses to identify infants and small children at an immediate risk to develop ECC, as well as by lay public and health professionals to identify high caries risk individuals and refer them to dentists for appropriate treatment. In addition, the proposed tests could be used for evaluating the effectiveness of preventive and clinical interventions in private dental practice, in research, and in community interventions, by comparing caries risk before and after the interventions.